Neonatal administration of the non-steroidal estrogen antagonists, Nafoxidine or Clomid, causes a hyperestrogenization syndrome which results in the production of abnormalities of the reproductive tract of the adult rat. These abnormalities include preneoplastic and neoplastic lesions. The histopathology of this syndrome will be further examined and the ability of various estrogens to induce it will be compared. The developmental sequence and preneoplastic changes that occur in the reproductive tract and other estrogen sensitive tissues will be examined. The effect of neonatal estrogen stimulation on reproductive physiology of the animals will be examined by measuring steroid and gonadotropin hormones in the blood during development. Hyperestrogenization also stimulates the formation of nuclear bodies in uterine epothelial cells. The formation of these nuclear bodies will be studied in relation to estrogen receptor binding, transcriptional activity and abnormal cell development. The ability of progesterone to inhibit nuclear body formation and abnormal cell growth will also be examined. The nuclear bodies will be characterized by enzymatic and autoradiographic methods. Isolation will be done by differential gradient centrifugation and gel filtration. Further characterization of the nuclear bodies will be examined by direct biochemical analysis and cDNA hybridization. Estrogen receptor binding to nuclear bodies will be related to other nuclear compartments.